Atezolizumab (A), cobimetinib (C), and vemurafenib (V) in patients (pts) with <i>BRAF</i><sup>V600</sup> mutation–positive melanoma with central nervous system (CNS) metastases (mets): Primary results from phase 2 Tricotel study.
Authors: Reinhard Dummer, Paola Queirolo, Ana Maria Abajo Guijarro, Youyou Hu, Dao Wang, Sergio Jobim Azevedo, Caroline Robert, Paolo Antonio Ascierto, Vanna Chiarion -Sileni, Paolo Pronzato, Francesco Spagnolo, Karmele Mujika, Gabriella Liszkay, Luis de la Cruz Merino, Hussein A. Tawbi
Journal: Journal of Clinical Oncology (2022)

9515 Retraction The abstract by Dummer et al entitled, “Atezolizumab (A), cobimetinib (C), and vemurafenib (V) in patients (pts) with BRAF V600 mutation–positive melanoma with central nervous system (CNS) metastases (mets): Primary results from phase 2 Tricotel study,” ( Journal of Clinical Oncology 40, no. 16, suppl 9515) published on June 2, 2022, has been retracted due to corrected data that has led to a change in the conclusions of the abstract. The updated results have been published online by Lancet Oncology in July 2023. See Dummer R, Queirolo P, Gerard Duhard P, et al: Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol doi: 10.1016/S1470-2045(23)00334-0. This abstract was retracted on August 7, 2023. Background: Despite recent advances in the treatment of melanoma, there remains an urgent need to improve outcomes in pts with CNS mets. To date, studies evaluating intracranial activity of immunotherapies and targeted therapies have included limited numbers of pts with symptomatic CNS mets. Cohort 2 of the phase 2 Tricotel study evaluated the safety and efficacy of A + C + V in BRAF V600 -mutated melanoma with CNS mets, including symptomatic pts receiving corticosteroids. Methods: Eligible pts were aged ≥18 y and had melanoma, MRI-confirmed CNS mets ≥5 mm in ≥1 dimension, and no prior systemic treatment for metastatic disease. Pts received A (840 mg on days 1 and 15 of each 28-d cycle) + C (60 mg once daily for 21 d on, 7 d off) + V (720 mg twice daily) except in cycle 1, during which A was withheld. Primary outcome was intracranial objective response rate (ORR; confirmed by assessments ≥4 wk apart per independent review committee [IRC]). Secondary end points were investigator-assessed intracranial ORR, extracranial ORR, overall ORR, duration of response (DOR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety. Prespecified subgroup analyses were performed in pts receiving corticosteroids (&gt;2 mg/d dexamethasone) and/or with CNS-related symptoms at baseline vs asymptomatic pts. Results: This study enrolled 65 pts (median age, 55 y; 63% male). At baseline, 37% were on corticosteroids and/or were symptomatic; 49% had elevated lactate dehydrogenase. Median follow-up was 9.7 mo for all pts, 10.0 mo for pts on corticosteroids and/or symptomatic at baseline (n = 24), and 9.7 mo for asymptomatic pts (n = 41). Intracranial ORR was 42% by IRC and 51% by investigator (BOR concordance: 68%). Intracranial DOR and PFS are listed in the Table. In pts on corticosteroids and/or symptomatic at baseline, ORR was 58%, DOR was 10.2 mo, and PFS was 7.2 mo by investigator; in asymptomatic pts, ORR was 46%, DOR was 5.7 mo, and PFS was 5.5 mo. Additional secondary efficacy end points will be presented. In 60 pts who received A + C + V, grade 3/4 adverse events (AEs) occurred in 70% of pts; most commonly lipase increased (27%) and blood CPK increased (17%). Serious AEs occurred in 30% of pts. AEs led to discontinuation of any study treatment in 27% of pts. Conclusions: Addition of A to C + V provides promising intracranial activity in pts with BRAF V600 -mutated melanoma with CNS mets, particularly in those receiving corticosteroids and/or in symptomatic pts. The safety profile of A + C + V is consistent with that observed in the IMspire150 study. Clinical trial information: NCT03625141. [Table: see text]